Japanese encephalitis is an infectious disease caused by infection with the Japanese encephalitis virus which is transmitted by mosquitoes such as Culex tritaeniorhyncus. The infection can occur even early after birth. The viral infection causes encephalopathy, leading to severe sequelae and high mortality rate. The immunity conferred by vaccination from early infancy is effective to prevent the disease. The Japanese encephalitis virus belongs to Flaviviridae. Vaccines used for preventing Japanese encephalitis have been produced and are commercially available. Japanese encephalitis vaccination is included in the routine vaccination in Japan. Based on the type of production method, Japanese encephalitis vaccines are categorized into vaccines produced by the mouse brain method and vaccines produced by the cell culture method. Also, there are inactivated Japanese encephalitis vaccines and attenuated live Japanese encephalitis vaccines. As for the dosage form, liquid vaccines and lyophilized vaccines have been produced and are commercially available. The theory of inactivated Japanese encephalitis vaccines produced by the mouse brain method is briefly described below.
The first Japanese encephalitis vaccine, which was a mouse brain-derived vaccine, was put to practical use in 1954. However, it was pointed out that the purity was low and there was a risk of vaccine inducing allergic central nervous system disorders. Subsequently, constant improvements were made to further purify the virus. An improved Japanese encephalitis vaccine with higher quality was put to practical use in 1965. The production techniques have been used up to the present date.
As mentioned above, inactivated Japanese encephalitis vaccines produced by the mouse brain method are highly pure and effective. However, it has been pointed out that the inactivated Japanese encephalitis vaccines have problems in safety and storage stability.
In view of the presently required safety level, there is a safety problem that because the vaccines are produced using mice housed in an insufficiently controlled environment, the possibility of adventitious agents being contaminated in vaccine products cannot be ruled out. Basically, this problem can be solved by using the cell culture-based production method. Recently, vaccines produced by the cell culture method have drawn attention all over the world, and there is a worldwide demand for vaccines in both advanced and developing countries. To solve the storage stability problem, gelatin has been added to vaccines as a stabilizer. However, it was pointed out that gelatin has the risk of inducing allergic reactions, and has become less frequent as a stabilizer. An alternative method to secure storage stability is to manufacture lyophilized products, and they can be stored for a long period in a cold room. However, the production cost of lyophilized products is high. Also, lyophilized products have the disadvantage of high storage cost, since cold-room or frozen storage requires storage facilities and devices such as refrigerators.
In conclusion, the efficacy, safety, and storage stability of inactivated Japanese encephalitis vaccines are summarized as follows. The efficacy is relatively satisfactory. The safety problem can be solved by developing a cell culture-based production method. The storage stability problem may be solved by using the lyophilization method; however, this method has the disadvantage of high production cost, while the storage stability of liquid products is not secured. That is, there is a demand for a new Japanese encephalitis vaccine that can be stored stably for a long period.
For another reason, improvement of the storage stability of liquid products is needed. Liquid products are usually inoculated by injection. In areas without sufficient medical facilities or specialists, there is a demand for supply of stable liquid Japanese encephalitis vaccine products that are used for transnasal or transdermal inoculation.
There is a need to develop not only Japanese encephalitis vaccines but also other viral vaccines that are excellent in the storage stability while maintaining low production costs.
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